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Ritodrine increases leukotriene B4 concentrations in pregnant sheep
1Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine.
Objectives:
Our goals were (1) to determine if beta-adrenergic receptor stimulation leads to 5-lipoxygenase metabolism of arachidonic acid and (2) to determine if inhibition of prostaglandin synthase alters 5-lipoxygenase metabolism of arachidonic acid during beta-adrenergic stimulation.
Study Design:
We infused saline solution, ritodrine (4 micrograms/kg/min), and a combination of ritodrine (4 micrograms/kg/min) and ketorolac (1.2 microgram/kg/min) into chronically catheterized pregnant sheep (gestational ages 110 to 120 days, term 147 days). With a radioimmunoassay we measured concentrations of leukotriene B4, a 5-lipoxygenase metabolite of arachidonic acid, in uterine venous and arterial plasma at 0, 2, and 4 hours during the infusion.
Results:
Both uterine venous and arterial leukotriene B4 were increased during ritodrine infusion (mean uterine venous increase at 2 hours 218%, p < 0.05; mean arterial increase at 2 hours 280%, p < 0.05). Concentrations during combined infusion of ritodrine and ketorolac increased significantly but were not different than concentrations observed during ritodrine infusion.
Conclusion:
Infusion of the beta-agonist ritodrine leads to 5-lipoxygenase metabolism of arachidonic acid and increased concentrations of leukotriene B4. The increased concentration in both uterine venous and arterial plasma suggests a systemic source of leukotriene B4 production. Concurrent inhibition of prostaglandin synthase during ritodrine infusion does not change 5-lipoxygenase metabolism in this model.